Reduced sirtuin 1/adenosine monophosphate-activated protein kinase in amyotrophic lateral sclerosis patient-derived mesenchymal stem cells can be restored by resveratrol

초록

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neuron system. Our previous study has shown that bone marrow-mesenchymal stem cells (BM-MSCs) from ALS patients have functional limitations in releasing neurotrophic factors and exhibit the senescence phenotype. In this study, we examined sirtuin 1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) activities and identified significant decreases in the ALS-MSCs compared with normal healthy control originated BM-MSCs. This decline was restored by pretreatment with resveratrol (RSV), measured using quantitative polymerase chain reaction, NAD/NADH assay, and immunoblot analysis. Neuroprogenitor markers were increased in RSV-treated ALS-MSCs (RSV/ALS-MSCs). The differentiated ALS-MSCs (ALS-dMSCs) exhibited a cell body and dendritic shape similar to neurons. RSV/ALS-MSCs showed significantly increased differentiation rate as compared with the untreated ALS-dMSCs. The neurite numbers and lengths were also significantly increased. This was confirmed with immunoblot analysis using neuron specific markers such as nestin, NF-M, Tuj-1, and Map-2 in RSV/ALS-dMSCs. Thus, this study shows that ALS-MSCs showed down-regulation of AMPK/SIRT1 signalling, which was recovered by treatment with RSV. This data suggest that RSV can be one of the candidate agents for improving therapeutic efficacy of ALS patients' originated MSCs.

키워드